The isolated perfused heart and the isolated beating cardiac myocyte will be used to assess the effects of cardiac hypertrophy on myocardial substrate utilization and high energy phosphate stores. Hearts of rats with either genetically determined or pressure overload induced cardiomegaly will be examined to determine their capacity to utilize glucose, fatty acids, lactate and amino acids. The metabolism of the various substrates will be assessed using radioisotope techniques and chemical analysis of tissue, perfusate and incubation media. In the perfused heart studies, the effects of pressure development, hormones ions and competitive substrates will be studied. Concurrently, the same studies will be performed on isolated cardiac myocytes obtained from normal and hypertrophied hearts. By measuring the same parameters in the whole heart and the isolated working (muscle) elements it is hoped to be able to differentiate between the effects which might be due to the proliferation of connective tissue such as hypoxia or impaired extracellular transfer of substrate, from the direct effects of hypertrophy on the muscle cells themselves. The proposed study should have two benefits: (a) it should aid in the elucidation of the roles played by alterations in myocardial metabolism, membrane permeability and high energy phosphate stores in the heart failure which develops in the terminal stages of the hypertrophic process and (b) it should help in characterizing the isolated cardiac myocyte preparation by providing a direct comparison with similiar measurements made in the more conventional perfused heart.